RESUMO
OBJECTIVE: To assess the utility of hepcidin, a potent regulator of host defense and inflammation, in the diagnosis of late-onset sepsis in very low birth weight infants. STUDY DESIGN: We compared the diagnostic performance of hepcidin with C-reactive protein from the serum concentrations in acute and convalescent blood specimens obtained from 44 infants suspected of late-onset sepsis. The predictive accuracies were assessed from the areas under receiver operating characteristic curves and the cutoffs that differentiated infants with and without sepsis were identified using classification and regression tree analysis. RESULTS: Seventeen of the enrolled infants in this study were bacteremic and/or received antibiotics for neonatal sepsis for ≥ 5 days (infants with sepsis). The concentrations of hepcidin were increased 4-fold in infants with compared with infants without sepsis (P < .0001) and returned to similar levels following therapy. The areas under receiver operating characteristic curves of hepcidin was 0.93 compared with 0.83 for C-reactive protein, P = .06. Hepcidin concentration >92.2 ng/mL correctly classified 91% of all infants (positive predictive value: 100%, negative predictive value: 87%, specificity: 100%, and sensitivity: 76%). CONCLUSION: Serum hepcidin concentration may be a useful adjunct test, in addition to blood culture and other markers of infection, in the evaluation of late-onset sepsis in very low birth weight infants.
Assuntos
Peptídeos Catiônicos Antimicrobianos/sangue , Sepse/sangue , Sepse/diagnóstico , Idade de Início , Biomarcadores/sangue , Proteína C-Reativa/análise , Feminino , Hepcidinas , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Masculino , Valor Preditivo dos TestesRESUMO
PURPOSE: KCNQ2 mutations have been found in patients with benign familial neonatal seizures, myokymia, or early onset epileptic encephalopathy (EOEE). In this study, we aimed to delineate the clinical spectrum of EOEE associated with KCNQ2 mutation. METHODS: A total of 239 patients with EOEE, including 51 cases with Ohtahara syndrome and 104 cases with West syndrome, were analyzed by high-resolution melting (HRM) analysis or whole-exome sequencing. Detailed clinical information including electroencephalography (EEG) and brain magnetic resonance imaging (MRI) were collected from patients with KCNQ2 mutation. KEY FINDINGS: A total of nine de novo and one inherited mutations were identified (two mutations occurred recurrently). The initial seizures, which were mainly tonic seizures, occurred in the early neonatal period in all 12 patients. A suppression-burst pattern on EEG was found in most. Only three patients showed hypsarrhythmia on EEG; eight patients became seizure free when treated with carbamazepine, zonisamide, phenytoin, topiramate, or valproic acid. Although the seizures were relatively well controlled, moderate-to-profound intellectual disability was found in all except one patient who died at 3 months. SIGNIFICANCE: De novo KCNQ2 mutations are involved in EOEE, most of which cases were diagnosed as Ohtahara syndrome. These cases showed distinct features with early neonatal onset, tonic seizures, a suppression-burst EEG pattern, infrequent evolution to West syndrome, and good response to sodium channel blockers, but poor developmental prognosis. Genetic testing for KCNQ2 should be considered for patients with EOEE.
Assuntos
Epilepsia/genética , Predisposição Genética para Doença/genética , Canal de Potássio KCNQ2/genética , Mutação/genética , Análise Mutacional de DNA , Eletroencefalografia , Epilepsia/fisiopatologia , Éxons/genética , Feminino , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: Preterm infants are often fed pasteurized donor milk or mother's milk that has been stored frozen for up to 4 weeks. Our objectives were to assess the impact of pasteurization or prolonged storage at -20 degrees C on the immunologic components of human milk and the capability of the different forms of human milk to support bacterial proliferation. MATERIALS AND METHODS: The concentrations and activities of major host defense proteins in the whey fractions of mother's milk stored for 4 weeks at -20 degrees C or pasteurized human donor milk were compared with freshly expressed human milk. Proliferation of bacteria incubated in the 3 forms of human milk was assessed. RESULTS: Relative to freshly expressed human milk, the concentrations of lysozyme, lactoferrin, lactoperoxidase, and secretory immunoglobulin A were reduced 50% to 82% in pasteurized donor milk and the activities of lysozyme and lactoperoxidase were 74% to 88% lower (P < 0.01). Proliferation of bacterial pathogens in pasteurized donor milk was enhanced 1.8- to 4.6-fold compared with fresh or frozen human milk (P < 0.01). CONCLUSIONS: The immunomodulatory proteins in human milk are reduced by pasteurization and, to a lesser extent, by frozen storage, resulting in decreased antibacterial capability. Stringent procedure to minimize bacterial contamination is essential during handling of pasteurized milk.
Assuntos
Manipulação de Alimentos/métodos , Microbiologia de Alimentos , Fatores Imunológicos/metabolismo , Proteínas do Leite/metabolismo , Leite Humano/imunologia , Esterilização/métodos , Adulto , Feminino , Temperatura Alta , Humanos , Imunoglobulina A/análise , Fatores Imunológicos/análise , Lactoferrina/análise , Lactoperoxidase/análise , Lactoperoxidase/metabolismo , Proteínas do Leite/análise , Leite Humano/química , Leite Humano/microbiologia , Muramidase/análise , Muramidase/metabolismo , Adulto JovemRESUMO
Epidemiologic studies suggest that the incidence and severity of sepsis are ameliorated in patients on statins (3- hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) for cholesterol lowering indications. We sought to understand the mechanism underlying such protection and hypothesized that simvastatin would be protective in mice against acute infection with Staphylococcus aureus, the primary etiologic agent in sepsis. Mice were treated with simvastatin or buffer for two weeks and were subsequently challenged with S. aureus intratracheally or intravenously. Relative to buffer-treated mice, bacterial killing was enhanced 4-fold (p=0.02), systemic dissemination was reduced, and lethality was decreased (hazard ratio 8.8, 95% CI 2.5 to 31.3, p=0.001) in mice that were pretreated with simvastatin for two weeks. Systemic inflammatory response was abrogated and the local elaboration of inflammatory mediators was diminished. Serum concentrations of pro-fibrinolytic protein C were elevated (p=0.034), while the concentration of pro-coagulant tissue factor in bronchoalveolar lavage fluids was attenuated (reduced 25%), p=0.001, in simvastatin-treated mice. Taken together, these data indicate that extended treatment with simvastatin is protective during infection with S. aureus through enhanced bacterial clearance, anti-inflammatory, and anti-coagulant activities. These studies provide insights into the mechanism by which statins confer protection in acute infection, support the notion that statins may be effective adjuncts in the treatment of sepsis, and provide a rationale for randomized control trials in patients that are at a high risk for infection characterized by coagulopathy.